Coronary artery disease may be one of the leading causes of morbidity and mortality in the industrialized nations. Vascular parameters, in particular shear stress acting on blood vessel walls, may play an important role in regulating the development of atherosclerosis, because shear stress may intimately modulate the biological activities of vascular endothelial cells (ECs), which line the inner lumen of blood vessels. Shear stress has been directly correlated with the distribution of focal atherosclerotic lesions in the arterial wall. Also, there is growing evidence that disturbed blood flow, or decreased wall shear stress associated with flow separation, favors the formation of arteriosclerosis.
Measurement of shear stress is thus important for the pathogenesis of coronary artery diseases. In addition, shear stress measurement may be important in order to study the durability of prosthetic valves, as well as to monitor platelet aggregation in cardiopulmonary bypass machines, and in artificial heart and left ventricular assist devices (LVADs). Diagnostically, luminal shear stress measurement may predict the development of atherosclerotic plaque in patients at risk for acute coronary syndrome. Further, luminal shear stress measurement may provide clinical information that can predict recurrent plaque formations in patients who have undergone intravascular stent deployment or bypass graft.
Measurement of wall shear stress, in particular near-wall shear stress, remains an engineering challenge, however. The wall shear stress as obtained from a laser Doppler velocimeter or a particle image velocimeter, may have an increased noise level, due to the reflection from the wall. Another challenge is the application of in-situ devices such as heated wires, which have to be employed close to the vessel wall to measure shear stress. Typically, the vessel wall may act as a potential heat sink, diverting the direction of convective heat transfer from the hot wires so that heat is conveyed to the vessel wall, instead of to the working fluid or blood. This causes a decrease in the sensitivity of the measurements.
Measuring temporal and spatial variations in shear stress, both of which have been implicated in the pathogenesis of atherosclerosis, is especially challenging. Micromachined MEMS (micro-electro-mechanical) sensors may provide possibilities for in-situ shear stress measurement, and for overcoming difficulties in measuring temporal and spatial variations in shear stress. Operating the MEMS sensors in a liquid environment, as may be necessary in many biomedical applications, may affect the sensitivity of the MEMS sensors. For example, MEMS sensors that are driven by front-side wire bonding may require insulation using sealants, which however may undergo expansion after prolonged exposure to the fluidic environment. Also, in MEMS sensors for which wire bonding is established on the front side, the elevation of microcircuitry on the same side of sensing element may disturb the local flow milieu, thus negatively affecting the precision of the shear stress measurement.
For these reasons, there is a need for improved methods and systems for precisely measuring real-time shear stress in microfluidic channels and microcirculation, as well as in large-scale arterial circulation.